Micro-muscle in biological medium

ABSTRACT

The invention concerns a micro-muscle designed to be immersed in a biological liquid, comprising a deformable chamber whereof one portion at least consists of a semipermeable membrane, said chamber containing a solution capable of osmotic activity. The solution is preferably activated by a product to be injected into the biological liquid.

[0001] The present invention relates to devices that can be used as atemporary or definitive actuator or endoprosthesis within a biologicalmedium such as the human body or an animal body.

[0002] The present invention especially finds applications as aring-shaped endoprosthesis or stent that can be used to compensate anarterial stenosis, or as an intervention means to aid the sewing,clipping, or jointing of blood vessels, to obturate a vessel, to fill upa cavity, or to have an element such as a needle act against an internalwall of a biological medium such as a human or animal body.

[0003] Inflatable balloons or shape-memory devices, which all exhibitdisadvantages, as will be discussed hereafter, are conventionally usedto perform such operations.

[0004] More specifically, the present invention provides a micromuscleintended to be immersed in a biological medium, comprising a deformablechamber having at least a portion formed of a semipermeable membrane,this chamber containing a solute likely to be osmotically active, thechamber being designed to have, after inflating by osmotic effect, apredetermined shape.

[0005] According to an embodiment of the present invention, the soluteis activable by a product injectable into the biological medium.

[0006] According to an embodiment of the present invention, the soluteis bound to an attachment matrix from which it can detach in consequenceof a competition with another body.

[0007] According to an embodiment of the present invention, the soluteis bound to HABA molecules, themselves bound to attachment matrixes byproteins, such as avidin or streptavidin derivatives, this bond beingbreakable by competition with biotin or the like.

[0008] According to an embodiment of the present invention, the soluteis bound to avidin molecules, themselves bound to attachment matrixes byHABA particles, this bond being breakable by competition with biotin orthe like.

[0009] According to an embodiment of the present invention, themolecules of biotin or the like are likely to be monomers or dimers.

[0010] According to an embodiment of the present invention, the soluteis encapsulated in at least one envelope to be destroyed by a physicalor chemical reaction.

[0011] According to an embodiment of the present invention, the soluteis formed of macromolecules likely to be broken by physical or chemicalaction.

[0012] According to an embodiment of the present invention, said chambercomprises a first portion made of a resilient material of desired shape,communicating with a second portion forming a semipermeable membrane,for example in the form of fibers.

[0013] According to an embodiment of the present invention, said chamberor its first resilient portion is torus-shaped.

[0014] According to an embodiment of the present invention, said chamberor its first resilient portion is likely to deform longitudinally.

[0015] According to an embodiment of the present invention, said chamberor its first resilient portion is a substantially spherical deformablevolume.

[0016] According to an embodiment of the present invention, said chamberunder its first resilient portion is formed of two half-cylinderssliding one inside of the other.

[0017] According to an embodiment of the present invention, said chamberor its first resilient portion is surrounded with sheath or netdetermining its definitive shape.

[0018] According to an embodiment of the present invention, the soluteis albumin.

[0019] According to an embodiment of the present invention, thesemipermeable membrane of the micromuscle is in communication with asecond chamber formed of a flexible material and containing a reserve ofa liquid likely to form a solution with a solute contained in the firstchamber.

[0020] According to an embodiment of the present invention, the secondchamber contains a solute likely to be released by physical or chemicalaction.

[0021] The present invention also provides a device for insertingneedles into a wall of a vessel filled with a biological liquid,comprising a guide, needles to which a wire is firmly attached on afirst side of the guide, the needles being likely to be laid flat on theguide, first osmotic micromuscles on the first side of the guide, likelyto erect the needles, and at least one second osmotic micromusclearranged on the opposite side of the guide.

[0022] The present invention also provides a device for aiding theclipping comprising a micromuscle insertable at the end of a cut upvessel, comprising a cylindrical body, digitized ends.

[0023] The present invention also provides a use of the above-mentionedmicromuscle, in which the micromuscle is torus-shaped and is intended tobe used as a joint at the connection between two ducts, such as acylindrical endoprosthesis and a blood vessel.

[0024] The present invention also provides a use of the above-mentionedmicromuscle, in which the micromuscle is torus-shaped, expandableoutwards and is intended to obturate a duct or a cylindricalendoprosthesis arranged in this duct.

[0025] The present invention also provides a use of the above-mentionedmicromuscle, in which the micromuscle is in the form of a bag orcylinder expandable outwards and is intended to obturate a duct.

[0026] The foregoing objects, features, and advantages of the presentinvention will be discussed in detail in the following non-limitingdescription of specific embodiments in connection with the accompanyingdrawings, among which:

[0027]FIGS. 1A to 1C illustrate a first embodiment of a micromuscleaccording to the present invention;

[0028]FIGS. 2A to 2C illustrate a second embodiment of a micromuscleaccording to the present invention;

[0029]FIGS. 3A to 3C illustrate alternatives of a third embodiment of amicromuscle according to the present invention;

[0030]FIGS. 4A and 4B show a fourth embodiment of a micromuscleaccording to the present invention;

[0031]FIG. 5A shows a fifth embodiment of a micromuscle according to thepresent invention;

[0032]FIG. 5B shows a sixth embodiment of a micromuscle according to thepresent invention;

[0033]FIGS. 6A and 6B show a seventh embodiment of the presentinvention;

[0034] FIGS. 7 to 9 illustrate an example of application of the presentinvention to a end-to-side anastomosis operation;

[0035] FIGS. 10 to 12 illustrate an example of application of thepresent invention to a clipping operation; and

[0036]FIGS. 13A and 13B illustrate an example of application of thepresent invention to a vessel obturation operation.

[0037] The present invention provides a micromuscle or microengine thatcan operate in a biological medium. This micromuscle comprises a chamberformed at least partially of a semipermeable membrane enabling transferof a solution by osmosis and containing a solute likely to dissolve in afluid contained in the biological medium. The solute will be selected tobe unable to cross said semipermeable membrane. Its presence induces anosmotic pressure likely to cause liquid transfers towards the chamber;the solute will thus be said to be “osmotically active”.

[0038] The chamber may be placed in compressed or folded form in aselected area of a biological medium, for example, at a given level ofan artery, via a catheter or an endoscope. Once the micromuscle has beenarranged, molecules from the solution in which it is placed tend tocross the semipermeable membrane and the micromuscle takes a desiredshape under the effect of the penetration of a biological liquid, forexample, water, into the chamber.

[0039] Examples of micromuscle shapes and structures are given in FIGS.1 to 6.

[0040]FIG. 1A is a perspective view of a torus-shaped micromuscle inexpansion. At rest, this micromuscle has either a flattened and possiblyfolded shape such as shown in FIG. 1B or a compressed or reduced shapeas shown in FIG. 1C.

[0041]FIG. 2A is a side view of a micromuscle of cylindrical shape inexpansion. At rest, this micromuscle has either a flattened or possiblyfolded shape such as shown in FIG. 2B or a cylindrical shape ofcompressed or reduced volume as shown in FIG. 2C.

[0042] The chamber such as illustrated for example in FIGS. 1A and 2Amay be formed of a semipermeable membrane, possibly formed of a thinsemipermeable layer deposited on a porous or perforated supportmaterial. This membrane may be resilient or not. For example, to expandfrom the shape shown in FIG. 1B or 2B to the shape shown in FIG. 1A or2A, the chamber material needs not be resilient. However, in the case ofFIGS. 1C and 2C, the chamber material is a resilient material thatexpands as adapted.

[0043] Various means may be provided to control the final shape and/orthe chamber expansion. For example, the chamber will be provided withfibers or surrounded with a net to control its final shape afterexpansion (flowing of the liquid of the biological medium towards theinside of the chamber).

[0044] As illustrated in FIG. 3A, the chamber may be formed, on aportion of its surface, of a semipermeable non-expandable membrane,little or not deformable, the rest of its surface being made of adeformable and possibly resilient material connected to thesemipermeable membrane. A chamber 1, for example, torus-shaped, made ofa resilient material, may be used, the internal volume of whichcommunicates with the internal volume of fibers 2 such as the fiberscurrently used in hemodialysis operations. The liquid penetrating intofibers 2 will fill up chamber 1 and expand it under the effect of theosmotic pressure. This composite embodiment comprising a first portionformed of an elastic membrane, for example, made of the product soldunder trade name Silastic, and a second portion formed of asemipermeable membrane, possibly in the form of fibers, preferablyflexible, can adapt to most of the embodiments of the present inventionas should be noted by those skilled in the art.

[0045] The micromuscle may also be formed of closed fibers withsemipermeable walls, initially in a folded state, which tend tostraighten and stiffen under the effect of the osmotic pressure.

[0046] In FIG. 3B, fibers 2 are arranged within a deformabletorus-shaped chamber.

[0047] In FIG. 3C, fibers 2 are directly arranged within a cylindricalelement to which an expansion force is desired to be applied, forexample, a blood vessel. In both cases, the fibers, initially containingmolecules enable of crossing the membrane at a concentration greaterthan the concentration of the biological fluid in molecules themselvesunable to cross the membrane, will tend to inflate and straighten, andthus to centrifugally urge the surface surrounding it, once placed in abiological fluid. For the fibers to take, once stiffened, the helicoidalshape illustrated in FIG. 3C, they may be attached in places, possiblyslidably, before inflating, to a flexible sheath not shown or to thevessel walls.

[0048] In a first version, an assembly of parallel osmotic fibers issewn to the fabric that forms the wall. The path of any one of thesefibers has a spiral shape. When the pressure increases within the fiber,the latter will tend to maximize its volume, and will thus tend todecrease its radius of curvature. Both ends of the osmotic fiber arestrongly secured to a specific point of the wall. However, the sewing ofthe osmotic fiber to the wall is sufficiently loose for the fiber to beable to slide with respect to the wall. The internal diameter of thehelix may thus increase, and the wall will tend to expand. The shapetaken by the assembly will result from the balance of the centripetalforces exerted by the osmotic fibers and from the resistance against theexpansion exerted by the wall.

[0049] Various alterations of this version may be envisaged. Forexample, inextensible wires parallel to the generators of the cylinderformed by the wall may be attached in various fashions (sewing, gluing .. . ) thereto. The attachment is performed to create regular spacingsbetween the inextensible wires and the wall, through which the fibersmay pass. These inextensible wires may possibly be semi-rigid rods.

[0050] In a second version, the osmotic fibers are directly integratedinto the fabric, to the frame of which they take part. An assembly offibers, for example, made of Dacron, is arranged to form a series ofparallel wires. The osmotic fibers are then crossed with this series ofparallel wires. Various pattern shapes may be created by the crossing ofDacron fibers and osmotic fibers (for example, the osmotic fibers mayhave a helicoidal shape, an arrowhead shape . . . ). In an alternative,the fabric is only formed of osmotic fibers.

[0051] It should be noted that such a device may find applicationsoutside of the field of vascular endoprosthesis design. Indeed, a bagformed of such a fabric can behave as a pump, the motions of which areconditioned by the relative concentration of the liquid medium inside ofthe bag and of the internal medium of the fibers in osmotically activesubstances.

[0052]FIGS. 4A and 4B show a fourth embodiment of the present invention,respectively in a state where the micromuscle is contracted, such as itis when put into place, and in a state where it is expanded, after itsputting into place and the setting of the osmotic pressure within thechamber. Two half-cylinders 4 and 5 slide one inside of the other. Eachof half-cylinders 4 and 5 is closed at its end opposite to the otherhalf-cylinder. Within internal half-cylinder 4 are arranged one orseveral chambers with a semipermeable wall 6 within which are moleculesunable to cross the membrane, not shown. The opposite ends of the twohalf-cylinders are connected by a wire 7 to limit their extension. As anexample, the system in the folded state may have a diameter on the orderof 100 pm and a length on the order of from 1 to 3 mm, this length beingsubstantially twice in the unfolded state. The device of FIGS. 4A and 4Bmay be called a microengine, an active element such as a needle beinglinkable to one of its ends.

[0053]FIG. 5A shows another embodiment of the present invention in whichseveral torus-shaped osmotic micromuscles 8 according to the presentinvention are connected to one another by a net or flexible wires 9, forexample, made of Dacron. The toruses may be distant from one another, asshown, or adjacent.

[0054]FIG. 5B shows another example of a composite micromuscle, theelementary torus-shaped micromuscles being designated with referencenumeral 8 and the connection wires or nets with reference numeral 9.

[0055] It should be noted by those skilled in the art that themicromuscle according to the present invention is likely to have manyother embodiments, and especially many other shapes. It may for examplebe a bag likely to expand and to take the shape of internal walls of acavity in which it is placed, for example, to fill a cavity such as ananeurism of a brain vessel or other.

[0056] Various solutes, not harmful for the organism in case of a leak,may be used. A known solute is for example albumin, which is not letthrough by the hemodialysis membrane.

[0057]FIGS. 6A and 6B illustrate a seventh embodiment of the presentinvention, usable in particular when the micromuscle according to thepresent invention must be inserted into a possibly humid, but non-liquidbiological medium. In this case, it may no longer be possible to “pump”the water from the organism. A device comprising two chambers orcompartments E1 and E2 communicating through an osmotic membrane M isthen provided. In an initial state, compartment E2 contains a fluid andcompartment E1 contains a solute likely to dissolve into the fluid ofcompartment E2. Thus, as illustrated in FIG. 6B, compartment E1 willtend to “inflate” by penetration through membrane M of the fluidcontained in compartment E2, the solute contained into compartment E1dissolving in this fluid. Each of these compartments has a deformable,tight, and biocompatible external envelope. In the example of embodimentillustrated in FIGS. 6A and 6B, chamber E2 has, firmly attached to it, alarge number of tight fibers similar to hair or tentacles incapable ofobturating a duct or of exerting a force on its walls. However,compartment E1 will have not effect on the walls of a duct in which itis arranged in the “deflated” state illustrated in FIG. 6A, but it willhave an obturating or pressure effect in the “inflated” state shown inFIG. 6B. Compartment E1 may have any desired shape, for example, theshape of an inflatable bag illustrated in the drawings or a torus,cylindrical or other shape.

[0058] For an insertion into the human body, for example, into a duct orvessel which is desired to be obturated or on the walls of which anaction is desired to be exerted, the micromuscles of FIGS. 6A and 6Bwill first be placed into a catheter in compressed form, that is,compartment E1 will have a reduced volume, the fluid that it containsbeing pushed out by the pressure towards compartment E2. As soon as thedevice is put into place, compartment E1 is free to expand and the fluidcontained in compartment E2 fills in this compartment which then exertsa desired action in the medium in which it is placed.

[0059] Various alterations of this embodiment may be provided. Forexample, as will be described hereafter, compartment E1 may comprisemolecules trapped in a protective envelope or likely to chemically reactwith other molecules to be activated only when desired. Similarly,compartment E2 may contain non-free solute molecules likely to bereleased only as a consequence of a physical or chemical action. In thissecond case, it is possible to “deflate” compartment E1 after insertionand inflating.

[0060] Control of the Expansion of an Osmotic Micromuscle

[0061] According to an aspect of the present invention, a method forcontrolling the expansion of a micromuscle according to the presentinvention is provided. This control may be chemical or physical.

[0062] Chemical Control

[0063] According to an embodiment of this aspect of the presentinvention, the micromuscle may contain a solute A likely to react with abody B and to form therewith a solute C, the number of formed moleculesof solute C being larger than the number of molecules of solute Aconsumed upon reaction between A and B. Body B is capable of crossingthe semipermeable membrane and solutes A and C are incapable thereof.Body B is then injected into the biological medium, for example, bymeans of an injection needle. It should be understood that, byperforming successive injections, successive “inflatings” of themicromuscle can be performed. Thus, if for example an artery is desiredto be expanded, a light expansion may be performed, and subsequentlyincreased. The interval between two injections may be long and will bechosen according to the organism's reactions to the micromuscle.

[0064] An implementation of this embodiment is based on the concept of“competition” between chemical bodies. The principle is that a body Acan combine, for example, in non-covalent fashion, with two bodies B andC. If A and C are put together in a solvent, a complex A-C will thusform. If, now, B is introduced into the solution, and if B has a greater“affinity” for A than C's for A, B will “move” C: the C molecules willbe released, and a complex A-B will form.

[0065] This competition principle may be used to increase the osmoticforce, for example as follows. Derivatives of specific proteins, such asavidin or streptavidin, covalently bonded to “attachment matrixes” (anysolid body used as a support) are used. These proteins play the functionof body A for which a competition will occur between body B and body C.Proteins A have the specificity of being able to bind in non-covalentfashion with a molecule of small molecular weight, HABA(4-hydroxyazobenzene-2-carboxylic acid). Body C will be obtained by“grafting” the HABA on a molecule having a sufficient molecular weightnot to cross the semipermeable membrane. At the time of its introductioninto the organism, the chamber thus contains an attachment matrix, towhich is bound in non-covalent fashion, via proteins A, body C. C beingattached to the matrix is thus not in solution and has no osmoticeffect. A “biotin” derivative, which plays the role of body B, is thenintroduced into the organism. Biotin is a vitamin with a low molecularweight, naturally present in the organism. Biotin has the specificity ofhaving a very strong affinity for avidin and for streptavidin, muchstronger than HABA's affinity for these proteins. Thus, molecules ofbody C detach from the attachment matrix and form a solute that tends toincrease the solution pressure within the chamber.

[0066] A, as well as B, will be chosen to obtain a selective affinity ofB for A: these molecules will have a very strong reciprocal affinity,while natural biotin will have a lesser affinity for A. The lowmolecular weight of B will enable it to easily cross the semipermeablemembrane. The affinity of B for A will make it compete with C to set onA, thus releasing from the matrix the HABA, and thus, body C, which willthen be able to exert its osmotic effect.

[0067] It should be noted that it is possible to attach to the matrix,instead of a derivative of avidin or streptavidin, a derivative of HABA,provided to take as C the result of a fusion of a “large” molecule witha derivative of avidin or streptavidin. As in the preceding case, theinjection of a biotin analog will “release” C, by competition with HABA.

[0068] This alternative, in which C comprises an avidin or streptavidinderivative, has the advantage of enabling partial reversibility of thedesired osmotic effect. It is indeed known to generate moleculescomprising not a single site having an effect analogous to that ofbiotin, but two such sites. Call B′ such a molecule (which will becalled the “dimer” biotin analog form, as opposed to the previously-used“monomer” biotin analog form, which has a single attachment site for anavidin or streptavidin derivative). After C has been released from thematrix (by injection of a monomer biotin analog form), if a dimer biotinanalog form is injected, the dimer form will compete with the monomerform. If the dimer form concentration is sufficient, it will move themonomer form from the avidin or streptavidin derivative sites of C. Thiswill translate as the forming of C-B′-C complexes, thus reducing thenumber of molecules in solution, and thus the osmotic effect. Theprocess may be repeated, by injecting again in a sufficient quantity thebiotin analog monomer form. In this case, indeed, the competition willbecome favorable to the forming of C-B complexes, which increases backthe number of molecules in solution.

[0069] Although the method has been described to control the osmoticeffect of a micromuscle, it also applies to the controlled release ofactive principles, thus providing an alternative to “implantablesyringe” type devices. Such devices exist, and are formed of “tanks”containing the product. Said product is ejected from the tanks under theeffect of a physical power source (gas under pressure, osmotic pressure,breakage of the tank wall under the effect of ultrasounds . . . ). Thepreviously-described competition principle has in its application tosuch devices the advantage of enabling accurate control of the time whenthe active principle is released (which is an advantage with respect togas or osmotic effect syringes), and of not requiring use of any devicecapable of generating and of directing the external power source (whichis an advantage with respect to methods using, for example,ultrasounds). It is enough, to achieve this specific object, for body Cwhich will be released to be the active principle of which the releaseis desired to be controlled, and to be able to cross the chamber inwhich it is. As soon as the adequate competitor B is introduced into theorganism (for example, sublingually, by ingestion or by injection), itwill release body C, thus enabling it to diffuse into the organism andto express its medical effect.

[0070] It should be noted that, in this alternative of the presentinvention, the use of a matrix is no longer indispensable, since it isno longer aimed at controlling the osmotic effect. In this case, call Cthe result of the combination between the active principle and HABA, andcall A the result of the fusion between an avidin derivative and a“large” molecule. A and C, put together in the same solution, form anA-C complex. The device inserted into the organism comprises a chamberlimited by a membrane impermeable to A-C, but permeable to C, as well asto biotin derivative B. The introduction of B into the organism willmove C, which can thus diffuse into the organism.

[0071] It should further be noted that the chamber used is notnecessarily artificial. There indeed exist in the organism regions intowhich only certain very specific molecule sorts can penetrate. Thenatural frontiers of these regions can thus play the function of thepreviously-used semipermeable membrane. The cephalo-rachidian liquid isan example of such a region, which has the advantage of being easilyaccessible (for example, by lumbar puncture). Such a region can thus beused as a “tank” and an active principle C such as that discussed in thepreceding paragraph can be introduced thereinto, for example, bypuncture. Couple (C, B) will in this case be chosen so that B is likelyto reach the region of interest. It should be noted that, in thespecific case of the cerebrospinal liquid, the release of C will beperformed mainly into the areas of cerebrospinal liquid resorption,which are located in the brain. This is particularly advantageous if thepreferential activity of C expresses in the brain (L-DOPA, for example,which is a precursor of dopamin, used in the treatment of Parkinson'sdisease).

[0072] It should also be noted that an alternative of the exploitationof the competition properties provided by biotin derivatives may beimplemented. Consider a protein having a large internal cavity likely tobe used as a tank (such is for example the case for certain “chaperon”proteins such as GroEL, or ferritin). It is possible to configure thisprotein so that HABA molecules are located at the level of its“aperture” and so that the attachment of avidin or streptavidin proteinsis likely to close the cavity. Such a mechanism enables “encapsulating”a large amount of active principle molecules. The introduction of biotininto the organism moves part of the avidin “plugs”, thus releasing partof the encapsulated molecules. This system requires for the“tank-protein” and “plug-protein” complexes to be in a medium ensuringtheir stability and a protection of the immune system, and for thismedium to be sensitive to variations of the biotin ratio in the blood.Such conditions can be imposed in an artificial chamber isolated fromthe organism by an adequate membrane, or obtained in a natural chamberlike the cerebrospinal liquid.

[0073] It should finally be noted that the provided examples are basedon the specific case of the competition between biotin derivatives andavidin or streptavidin derivatives, but that the same results can beobtained with other systems of competition between molecules.

[0074] Physical Control

[0075] According to an embodiment of this aspect of the presentinvention, the control can be performed physically, for example byplacing part at least of the solute in one or several microcapsules sothat it has initially no or little activity. The microcapsules can thenbe broken, possibly selectively, by means of an external power source,for example, ultrasounds, a magnetic field, or a laser. A body likely todissolve the microcapsules may also be injected.

[0076] It should be noted that physical power may be directly used to“break” molecules into smaller molecules, which has an effect upon theosmotic properties of the solution thus performed. Macromolecules suchas DNA may be broken by the application of ultrasounds (this techniqueis commonly used in molecular biology). The longer the ultrasounds areapplied, the more the average fragment size decreases. In an alternativeof the present invention, large-size DNA fragments (obtained for exampleby any protocol of purification of the bacterial DNA, or by “polymerasechain reaction” from the genetic material of the individual to betreated) are placed inside of a semipermeable membrane chosen not to letthrough such large-size fragments. After the application of ultrasounds,the number of fragments and, accordingly, the osmotic force, increase.The membrane may be chosen to let through DNA fragments of sufficientlysmall size. In this case, a sufficiently prolonged application ofultrasounds enables releasing part of the DNA from within the membrane,and thus decreasing the osmotic force. It should however be noted thatin this alternative, the osmotic force cannot be increased backafterwards.

APPLICATION EXAMPIES

[0077] Various examples of applications of an osmotically-inflatablemicromuscle according to the present invention will now be described.

[0078] 1. Vascular Endoprostheses

[0079] Methods are known for treating an aneurism, that is, a loss ofthe parallelism of the edges of a vessel, which translates as anexpansion of a vascular segment, consisting of inserting into thevessel, at the expansion level, a cylinder, for example made of ashape-memory material, which is arranged to obturate the communicationbetween the vessel and the aneurism. However, the vessel appears inpractice to expand along time and the blood flowing through the vesselcan again communicate with the aneurism.

[0080] To solve this problem, the present invention provides using,instead of the shape-memory cylinder, a cylinder formed from an osmoticmicromuscle according to the present invention. According to analternative of the present invention, it is provided to use aconventional vascular endoprosthesis formed of a shape-memory material,and to arrange at both ends of this prosthesis a torus-shaped osmoticmicromuscle which will behave as a seal of variable and controllablediameter. Indeed, as indicated previously, it may be provided toprogressively inflate this torus-shaped micromuscle, at regularintervals, to take into account deformations of the vessel.

[0081] 2. Progressive Vascular Expansion

[0082] Known vessel expansion vascular methods are based on the use of“stents” or ring-shaped springs which are inserted inside of a bloodvessel at a location where said vessel is stenosed. Such stentsconventionally use memory-shape alloys and face the problem of“restenosis”, that is, after having being increased by the expansiongesture, the vessel diameter secondarily decreases, thus depriving thepatient of the benefit of the present invention.

[0083] The applicant considers that this restenosis is for the most partdue to the aggressive character of the expansion. Indeed, withconventional methods, this expansion is performed very rapidly, incertain cases within a few seconds for shape-memory stents and within afew minutes for mechanically-inflated stents. The vessel diameter can beincreased by a factor on the order of 2 or more. This results in aninflammatory reaction which will exert on the stent a constrictiveeffort sufficient to deform it.

[0084] The use of a torus-shaped micromuscle according to the presentinvention enables solving this problem, given that it can be adjusted tovery progressively “inflate”, for example, within several days. On theother hand, as indicated previously, successive methods for activatingthe micromuscle according to the present invention may be provided and,at regular intervals, for example, one week, one month or more, themicromuscle may be “reinflated” to perform a very progressive expansionof the vessel to be expanded.

[0085] A micromuscle according to the present invention may appear undera particularly small volume in the non-contracted state and can thuseasily be inserted by conventional means such as catheters or endoscopesat any desired location.

[0086] 3. Vessel Suture

[0087] 3.1. End-To-Side Anastomosis

[0088] Coronary artery bypass usually uses a derivation of an artery(for example, the internal mammary artery), which is mobilized andanastomosed just downstream of the stenosed area (end-to-sideanastomosis). The diameters of the thinnest coronaries on which suchgestures are performed are on the order of from 1.5 mm to 2 mm. Thepresent invention provides a device enabling sewing while respecting thepressure in the vessel (here, the coronary), to ease its handling.3.1.1. Preparation of the mammary The mammary artery may be “equipped”with various mechanisms intended to ease its anastomosis with thecoronary. It is indeed possible to introduce a catheter into the freeend of the mammary, and to inflate a small balloon around this catheter,which will enable attaching to this end the mechanisms adapted to thosewhich will subsequently equip the coronary (at the possible cost of thesubsequent sacrifice of the few vessel millimeters located downstream ofthe end balloon). 3.1.2. Forming of a “buttonhole” on the coronary Acatheter having dimensions smaller than one millimeter is introducedinto the coronary, at the level desired for the anastomosis. Thisintroduction can be performed through the femoral.

[0089] The catheter comprises a guide. This guide may be immobilized attwo points located upstream and downstream of the area to be anastomosed(by means of two clips seizing the coronary).

[0090] On guide 10 is assembled a “foldable harrow”. This harrow isillustrated in unfolded position in FIG. 7A. It is formed of two ranksof needles 11. The needle shapes and dimensions are those currently usedto enable sewing of the coronaries. Typically, their base diameter is onthe order of a few hundreds of micrometers, and their length is on theorder of a few millimeters. At their base, the needles are firmlyattached to a single wire 12. This wire defines two sub-assemblies of“right-hand” and “left-hand” needles. The wire first connects the“right-hand” needle assembly, the bases of which are aligned (or form avery elongated half-ellipse), then the “left-hand” needle assembly (seeFIG. 9).

[0091] The needles are arranged so that the harrow can take two limitingconfigurations. In the “catheter” configuration, illustrated in FIG. 7B,the needles are elongated along the catheter axis. In the “sewing”configuration, illustrated in FIG. 7A, the needles are perpendicular tothis axis. According to the present invention, the raising of the harrowuses at least one “osmotic motor” comprising a first small balloon 13arranged on the lower side of the harrow and one or several second smallballoons 14 arranged on the upper side of the harrow and arranged tosurround the needles. One or the other of osmotic motors 13 and 14 maybe replaced with its hydraulic or pneumatic equivalent.

[0092] Once the harrow is in place, to enable perforation of thecoronary, balloon 13 located under the harrow is “inflated” while“balloons” 14 intended to erect the needles keep their initial pressure.This then leads to the position illustrated in FIG. 8.

[0093] When an “osmotic” mechanism is used, these operations areimplemented in very natural fashion. The small balloons are indeeddeflated when the catheter is introduced. The latter may be protected bya cap, which avoids for these balloons to be in contact with a hydrousmedium. The removal of this cap puts the balloons in contact with theblood medium, which activates the osmotic mechanism. If, for example,the osmotically-active bodies have been introduced with a concentrationtwice smaller in balloons 14 intended to erect the needles than inballoon 13 intended to place these needles flat against the oppositewall, the needles will first erect, then be placed back against thewall, and finally perforate said wall. 3.1.3. Mammary and coronaryanastomosis The harrow needles must be used, once they have perforatedthe coronary wall.

[0094] The mammary may have been equipped with a mechanism enablingholding the needles (for example, triple collar, each needle passingbefore the first collar, behind the second one, and before the thirdone). The collars are then stretched, which firmly attaches the collarsto the needles.

[0095] The mammary may have been equipped with a mechanism equivalent tothe coronary's. The “coronary” needles must then be immovably attachedto the “mammary” needles. Various simple mechanisms can be envisaged(welding, gluing, “twisting” of one needle around the other, etc.).

[0096] It may also be devised for the “right-hand” needles to be allraised, to form a series of wire “bridges”, under which a cable havingits two ends attached to the mammary is introduced. The motions to beperformed are here very simple. When the “right-hand” needles have beenfirmly attached to the mammary, the same operation is performed for the“left-hand” needles.

[0097] 3.1.4. Opening of the Communication Between Mammary and Coronary

[0098] Up to this stage, the circulation in the coronary has not beeninterrupted, and the arterial circulation of the mammary is not yetconnected to the coronary's. However, the sewing is now ended. Thecoronary wall still has to be perforated, on its component locatedbetween the two rows of needles. The flow pressure will “round up” thisopening.

[0099] The perforation may be performed mechanically, from anintra-mammary catheter. It may also be electrically devised. Theintra-coronary catheter guide is indeed placed flat against the area tobe perforated. If it conducts the current, and if it is bare over thisarea (the rest being isolated), a current can flow through theintra-mammary catheter and the intra-coronary catheter, the assemblybehaving as an electric lancet.

[0100] The balloons are finally deflated, and the coronary and mammarycatheters can then be removed. 3.2. Osmotic clipping In vascularsurgery, clipping is an advantageous alternative to sewing, since itenables “confronting” two vessels without leaving material in contactwith the vascular bed. A mechanical stapler has been described by T.Richard in “AAA: Laparoscopic and/or endovascular repair?”,Angio-Techniques 2001. The vessel end is arranged on an “anvil”, whichenables turning over the free edge, and then having a sufficiently rigidsupport to enable bearing of the clips.

[0101] The disadvantages of this system are:

[0102] a relative complexity of the stapler,

[0103] the need to use an intermediary vascular substitute (indeed, thestapler must be able to “enter” through the free end of a vessel; thetwo terminal ends to be anastomosed are thus “equipped”, after which anadequate device enables restoring the continuity),

[0104] the difficulty of miniaturizing the system.

[0105] To overcome these disadvantages, the present invention providesan osmotic clipping device.

[0106] First, the free end of each vessel is prepared as follows. Anelastic “bag”, exhibiting on a portion at least of its surface asemipermeable membrane, is introduced into the vessel. This bag, wheninflated, has the shape illustrated in FIGS. 10A and 10B respectively inside view and in top view:

[0107] it has a rotational symmetry,

[0108] one of its ends 20 is cylindrical,

[0109] medium 21 is conical,

[0110] the other end comprises digitations 22.

[0111] As illustrated in FIGS. 11A to 1C, the bag is introduced while“deflated” into a vessel 24 (FIG. 11A). A ring 25 with as manyprotrusions 26 as there are intervals between the digitization isinstalled on vessel 24 (FIG. 11B). Finally, the bag is “inflated”.

[0112] The different steps of the assembling of two sections of a vesselare illustrated in FIGS. 12A to 12C. The two sections, equipped as thatshown in FIG. 1C, are shown opposite to each other as illustrated inFIG. 12A.

[0113] Care has been taken over the positioning of protuberances 26 ofrings 25 in the spaces left empty by digitizations 22. The protrusionssupported by one of the rings are the “male” portions of “press studs”,those supported by the other ring being the “female” portions of thesame “press studs”.

[0114] The protuberances are positioned opposite to one another, incomplementary fashion, and the rings are then brought close to eachother (FIG. 12B) before fastening the “press buttons” (FIG. 12C). Beforeblocking the last press button element(s), the bags are deflated (forexample, by being perforated by means of a needle). In their deflatedform, they may be extracted through the orifice remaining between thetwo vessels.

[0115] In the present section 3.2, only the case where the “bags”intended to expand the vessel orifices and to prepare the assembly ofthe rings provided with protrusions are of osmotic micromuscle type. Itshould be noted that pneumatically-inflating balloons or shape-memorydevices may also be used to perform this operation.

[0116] 4. Reversible Obtaration of a Vessel

[0117] A micromuscle according to the present invention may also be usedinside of a duct or vessel as a valve that may be opened or closed.

[0118] An embodiment of such a valve is illustrated in FIG. 13A in openposition and in FIG. 13B in closed position inside of a duct or vessel41. An endoprosthesis or stent of cylindrical shape 42 formed forexample of a shape-memory alloy is surrounded on its median portion witha sleeve 43 formed of a ring-shaped osmotic micromuscle arranged betweenthe cylinder and the vessel. In the case where the vessel walls areresilient, the stent diameter is selected to be slightly greater thanthat of the vessel to enable anchoring of the stent in the vessel. Theexpansion capacity of the micromuscle, upon contact with the vesselwall, makes it exert a radial force that compresses both the stent andthe wall. The respective forces exerted by the stent and by themicromuscle will be selected to result in the complete obturation of thevessel. One of the previously-described means may be used to stop thecompression effect exerted by the micromuscle and “reopen” the vessel.

[0119] Such a valve may for example be used for the reversibleobturation of the Fallopian tubes. Indeed, the ligature of the Fallopiantubes (natural duct with a diameter of a few millimeters linking theovaries to the uterus) is used as a contraceptive means. However, thistechnique results in a quasi-definitive sterilization, possible surgicalinterventions intended to restore the functionality of these tubeshaving a high failure ratio.

[0120] If a valve of the above-mentioned type is inserted into each ofthe two tubes, the device operates as a contraceptive means. Theintroduction of the stent into the tube may be carried out through thevagina or possibly by laparoscopy. When the woman wants to stop thiseffect, the tube functionality is simply restored.

[0121] It can be feared that the internal medium of the Fallopian tubes,though humid, is insufficiently liquid to have a direct action upon anosmotic micromuscle likely to attract a liquid from the surroundingmedium. In this case, it will be chosen to use a micromuscle accordingto the seventh embodiment of the present invention, illustrated inrelation with FIGS. 6A and 6B, which has its own liquid reserve. In thisapplication, a reversible micromuscle will preferably be used, that is,a micromuscle in which the second compartment is likely under the effectof a physical or chemical action to “deflate” the first compartment. Thecontraceptive action is then made reversible.

[0122] It should be noted by those skilled in the art that it is alsopossible to directly use the capacity of acting as a “plug” of theseventh embodiment of the present invention. In this case, themicromuscle is inserted into the Fallopian tube, that it obturates. Iflater the patient wants to have children again, one of thepreviously-described micromuscle control modes is applied and enablesdeflating compartment E1. Nothing then “blocks” the micromuscle anylonger in the Fallopian tube, and it naturally falls in the uterinecavity, from which it will be evacuated at the next menstrual period.This specific embodiment has the disadvantage of requiring a new settinginto place of the device, if the contraceptive function is subsequentlywanted back. It however has the advantage of not leaving a foreign bodyin the organism, which may pose psychological and physiological problems(the mobility of the tube wall is indeed a significant element of thefemale fertility, and the permanent presence of a stent could negativelyaffect it).

[0123] Among the many alterations and modifications of the presentinvention which will occur to those skilled in the art, it should benoted that most of the applications of osmotic micromuscles which havebeen described may be implemented by using devices having, in theseapplications, functions similar to those of the osmotic micromuscles,for example, pneumatic or shape-memory devices.

1. A micromuscle for immersion in a biological medium, comprising adeformable chamber having at least a portion formed of a semipermeablemembrane, this chamber containing a solute likely to be osmoticallyactive, the chamber being designed to have, after inflating by osmoticeffect, a predetermined shape.
 2. The micromuscle of claim 1, whereinthe solute is activable by a product injectable into the biologicalmedium.
 3. The micromuscle of claim 2, wherein the solute is bound to anattachment matrix from which it can detach in consequence of acompetition with another body.
 4. The micromuscle of claim 3, whereinthe solute is bound to HABA molecules, themselves bound to attachmentmatrixes by proteins, such as avidin or streptavidin derivatives, thisbond being breakable by competition with biotin or the like.
 5. Themicromuscle of claim 3, wherein the solute is bound to avidin molecules,themselves bound to attachment matrixes by HABA particles, this bondbeing breakable by competition with biotin or the like.
 6. Themicromuscle of claim 5, wherein the molecules of biotin or the like aremonomers or dimers.
 7. The micromuscle of claim 1, wherein the solute isencapsulated in at least one envelope to be destroyed by a physical orchemical reaction.
 8. The micromuscle of claim 1, wherein the solute isformed of macromolecules likely to be broken by physical or chemicalaction.
 9. The micromuscle of claim 1, wherein said chamber comprises afirst portion made of a resilient material of desired shape,communicating with a second portion forming a semipermeable membrane,for example in the form of fibers.
 10. The micromuscle of claim 1,wherein said chamber or its first resilient portion is torus-shaped. 11.The micromuscle of claim 1, wherein said chamber or its first resilientportion is capable of being longitudinally deformed.
 12. The micromuscleof claim 1, wherein said chamber or its first resilient portion is asubstantially spherical deformable volume.
 13. The micromuscle of claim1, wherein said chamber is formed of a fiber that stiffens afterinflating.
 14. The micromuscle of claim 1, wherein said chamber underits first resilient portion is formed of two half-cylinders sliding oneinside of the other.
 15. The micromuscle of claim 1, wherein saidchamber or its first resilient portion is surrounded with sheath or netdetermining its definitive shape.
 16. The micromuscle of claim 1,wherein the solute is albumin.
 17. The micromuscle of claim 1, whereinthe semipermeable membrane (M) of the micromuscle is in communicationwith a second chamber (E2) formed of a flexible material and containinga reserve of a liquid likely to form a solution with a solute containedin the first chamber (E1).
 18. The micromuscle of claim 17, wherein thesecond chamber contains a solute likely to be released by physical orchemical action.
 19. A device for inserting needles into a wall of avessel filled with a biological liquid, comprising: a guide (10),needles (11) to which a wire (12) is firmly attached on a first side ofthe guide, the needles being likely to be laid flat on the guide, firstosmotic micromuscles (14) of claim 1 on the first side of the guide,likely to erect the needles, and at least one second osmotic micromuscle(13) of claim 1 arranged on the opposite side of the guide.
 20. A devicefor aiding the clipping comprising a micromuscle of claim 1 insertableat the end of a cut up vessel, comprising: a cylindrical body (20), anddigitized ends (22).